Incommensurate chirality density wave transition in a hybrid molecular framework

Using single-crystal X-ray diffraction we characterise the 235\,K incommensurate phase transition in the hybrid molecular framework tetraethylammonium silver(I) dicyanoargentate, [NEt$_4$]Ag$_3$(CN)$_4$. We demonstrate the transition to involve spontaneous resolution of chiral [NEt$_4$]$^+$ conformations, giving rise to a state in which molecular chirality is incommensurately modulated throughout the crystal lattice. We refer to this state as an incommensurate chirality density wave (XDW) phase, which represents a fundamentally new type of chiral symmetry breaking in the solid state. Drawing on parallels to the incommensurate ferroelectric transition of NaNO$_2$ we suggest the XDW state arises through coupling between acoustic (shear) and molecular rotoinversion modes. Such coupling is symmetry-forbidden at the Brillouin zone centre but symmetry-allowed for small but finite modulation vectors $\mathbf q=[0,0,q_z]^\ast$. The importance of long-wavelength chirality modulations in the physics of this hybrid framework may have implications for the generation of mesoscale chiral textures, as required for advanced photonic materials.Comment: 5 pages, 3 figure

Routes to Advanced Intermediates in the Synthesis of Tetracarbocyclic Sesquiterpenoids Daphnenoid A and Artatrovirenols A and B

A short route from dihydrocarvone is described, which led to the tetracarbocyclic core common to artatrovirenol A and B and daphnenoid A. A variant of this route afforded guaia-4,6-dien-3-one (from Enterospermum madagascarensis) and its epimer. From 2-(2-oxoethyl)­furan, a 15-step sequence then delivered the complete carbon skeleton and all functionality necessary for daphnenoid A. Key steps in the route include diastereoselective intramolecular oxidopyrylium cycloaddition, oxa-bridge cleavage under “push–pull” conditions, and intramolecular Diels–Alder cycloaddition

Asymmetric Synthesis of Nortropanes

Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here, we report Rh-catalyzed asymmetric Suzuki–Miyaura-type cross-coupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero)aryl boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N-, O-, and S-containing nucleophiles. The method was applied in a highly stereoselective formal synthesis of YZJ-1139(1), a potential insomnia treatment that recently completed Phase II clinical trials. Our report represents an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds

Anthracene-porphyrin nanoribbons

π-Conjugated nanoribbons attract interest because of their unusual electronic structures and charge-transport behavior. Here, we report the synthesis of a series of fully edge-fused porphyrin-anthracene oligomeric ribbons (dimer and trimer), together with a computational study of the corresponding infinite polymer. The porphyrin dimer and trimer were synthesized in high yield, via oxidative cyclodehydrogenation of singly linked precursors, using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and trifluoromethanesulfonic acid (TfOH). The crystal structure of the dimer shows that the central π-system is flat, with a slight S-shaped wave distortion at each porphyrin terminal. The extended π-conjugation causes a dramatic red-shift in the absorption spectra: the absorption maxima of the fused dimer and trimer appear at 1188 nm and 1642 nm, respectively (for the nickel complexes dissolved in toluene). The coordinated metal in the dimer was changed from Ni to Mg, using p-tolylmagnesium bromide, providing access to free-base and Zn complexes. These results open a versatile avenue to longer π-conjugated nanoribbons with integrated metalloporphyrin units

Bifunctional iminophosphorane catalyzed amide enolization for enantioselective cyclohexadienone desymmetrization.

The organocatalytic enolization of 2-arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5-cyclohexadienones, yielding 3D fused N-heterocycles, is described. The transformation represents the first strong activating group-free activation of carboxamides via α-C-H deprotonation in a metal-free, catalytic, and enantioselective reaction, and is achieved by employing a bifunctional iminophosphorane (BIMP) superbase

Iridium-catalysed synthesis of C, N, N -cyclic azomethine imines enables entry to unexplored nitrogen-rich 3D chemical space

Three-dimensional nitrogen-rich bridged ring systems are of great interest in drug discovery owing to their distinctive physicochemical and structural properties. However, synthetic approaches towards N–N-bond-containing bridged heterocycles are often inefficient and require tedious synthetic strategies. Here we delineate an iridium-catalysed reductive approach to such architectures from C, N, N-cyclic hydrazide substrates using IrCl(CO)[P(OPh)3]2 and 1,1,3,3-tetramethyldisiloxane (TMDS), which provided efficient access to the unstabilized and highly reactive C, N, N-cyclic azomethine imine dipoles. These species were stable and isolable in their dimeric form, but, upon dissociation in solution, reacted with a broad range of dipolarophiles in [3 + 2] cycloaddition reactions with high yields and good diastereoselectivities, enabling the direct synthesis of nitrogen-rich sp3-hybridized pyrazoline polycyclic ring systems. Density functional theory calculations were performed to elucidate the origin of the diastereoselectivity of the cycloaddition reaction, and principal moment of inertia (PMI) analysis was conducted to enable visualization of the topological information of the dipolar cycloadducts

Total synthesis and structure confirmation of (E) and (Z)-ocellenyne

The (E/Z)-ocellenynes are C15 dibrominated Laurencia natural products whose structures have been subject to several reassignments on the basis of extensive NMR analysis, biosynthetic postulates, and DFT calculations. Herein, we report the synthesis of both (E)- and (Z)-ocellenyne, which, in combination with single crystal X-ray diffraction studies, allows their absolute configuration to be established and defines the configuration of the syn-12,13-dibromide as being (S, S) in keeping with their proposed biogenesis from the (6S, 7S)-laurediols

αβ,α'β'-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes

Epoxides are an established class of electrophilic alkylating agents that react with nucleophilic protein residues. We report αβ,α′β′-diepoxyketones (DEKs) as a new type of mechanism-based inhibitors of nucleophilic cysteine enzymes. Studies with the L,D-transpeptidase LdtMt2 from Mycobacterium tuberculosis and the main protease from SARS-CoV-2 (Mpro) reveal that following epoxide ring opening by a nucleophilic cysteine, further reactions can occur, leading to irreversible alkylation

Enantioselective Synthesis of Sealutomicin C

The sealutomicins are a family of anthraquinone antibiotics featuring an enediyne (sealutomicin A) or Bergman-cyclized aromatic ring (sealutomicins B–D). Herein we report the development of an enantioselective organocatalytic method for the synthesis of dihydroquinolines and the use of the developed method in the total synthesis of sealutomicin C which features a transannular cyclization of an aryllithium onto a γ-lactone as a second key step

GPs’ strategies in exploring the preschool child’s wellbeing in the paediatric consultation

Background: Although General Practitioners (GPs) are uniquely placed to identify children with emotional, social, and behavioural problems, they succeed in identifying only a small number of them. The aim of this article is to explore the strategies, methods, and tools employed by GPs in the assessment of the preschool child’s emotional, mental, social, and behavioural health. We look at how GPs address parental care of the child in general and in situations where GPs have a particular awareness of the child. Method: Twenty-eight Danish GPs were purposively selected to take part in a qualitative study which combined focus-group discussions, observation of child consultations, and individual interviews with GPs. Results: Analysis of the data suggests that GPs have developed a set of methods, and strategies to assess the preschool child and parental care of the child. They look beyond paying narrow attention to the physical health of the child and they have expanded their practice to include the relations and interactions in the consultation room. The physical examination of the child continues to play a central role in doctor-child communication. Conclusion: The participating GPs’ strategies helped them to assess the wellbeing of the preschool child but they often find it difficult to share their impressions with parents